Edgewise Therapeutics Reports Positive Results from Phase 1 and Phase 2 HCM Trials

Edgewise Therapeutics has reported encouraging top-line results from both Phase 1 studies in healthy subjects and the Phase 2 CIRRUS-HCM trial in patients with obstructive hypertrophic cardiomyopathy (HCM). The drug under investigation, EDG-7500, is an oral, selective cardiac sarcomere modulator designed to slow early contraction velocity and improve cardiac relaxation in HCM.

The Phase 1 trial involved healthy subjects who received varying doses of EDG-7500. In the single ascending dose (SAD) part of the trial, 48 participants received doses ranging from 5 to 300 mg. In the multiple ascending dose (MAD) segment, 24 subjects were administered doses between 25 and 100 mg daily over 14 days. EDG-7500 was well tolerated in both segments, with no significant changes noted in vital signs, clinical chemistry, hematology, or electrocardiograms. Importantly, there were no meaningful changes in left ventricular ejection fraction (LVEF) across the different dose ranges. The drug exhibited a half-life of about 30 hours and reached a steady state within four days of daily dosing. Dose-proportional increases in exposure were observed in both SAD and MAD phases.

In the CIRRUS-HCM trial's Part A phase, patients with obstructive HCM received single doses of 50, 100, or 200 mg of EDG-7500. The results were promising, showing a 67% average reduction in resting left ventricular outflow tract (LVOT) pressure gradient and a 55% reduction in provokable (Valsalva) LVOT gradient for those on 100 and 200 mg doses. Additionally, 60% of subjects receiving these doses had LVOT gradients of less than 30 mmHg at rest and below 50 mmHg with Valsalva. These improvements were achieved without significant changes in LVEF. A single dose of 200 mg led to a 64% reduction in NT-proBNP levels, a key biomarker for heart failure, indicating the potential for treating diseases characterized by diastolic dysfunction, such as non-obstructive HCM.

In both the Phase 1 and CIRRUS-HCM trials, no patients experienced a reduction in LVEF to below 50% across the varying doses of EDG-7500.

Dr. Marc Semigran, Chief Development Officer at Edgewise Therapeutics, stated that based on the solid clinical and preclinical data, the company has initiated the 28-day phase of CIRRUS-HCM involving patients with both obstructive and non-obstructive HCM. This phase aims to further assess tolerability, pharmacokinetics, and the effects on LVOT-G, LVEF, biomarkers, and overall patient well-being. Dr. Anjali T. Owens from the University of Pennsylvania emphasized the unmet medical needs of HCM patients and expressed excitement over participating in the ongoing CIRRUS-HCM trial.

Dr. Kevin Koch, President and CEO of Edgewise Therapeutics, highlighted the potential of EDG-7500 in providing gradient relief without reducing LVEF, which could be a significant advancement in treating obstructive HCM. The company anticipates releasing initial 28-day data in the first quarter of 2025.

EDG-7500 is designed to address the impaired cardiac relaxation associated with hypertrophic cardiomyopathy and other diastolic dysfunction diseases. The CIRRUS-HCM trial is a three-part, multicenter, open-label study involving around 55 HCM patients across up to 20 clinical sites in the United States. Part A's primary goal was to assess the safety and tolerability of a single EDG-7500 dose, while Parts B and C will evaluate the effects of multiple doses over 28 days in obstructive and non-obstructive HCM patients.

Hypertrophic Cardiomyopathy (HCM) affects roughly one in 500 people and is linked to diminished quality of life and elevated risks of heart failure, abnormal heart rhythms, and sudden cardiac death. It is characterized by excessive contraction and thickening of the heart's left ventricular wall, leading to diastolic dysfunction. Despite treatment advancements, there remains a significant need for new therapeutic options.

Edgewise Therapeutics specializes in developing treatments for serious muscle and cardiac conditions. The company's portfolio includes EDG-7500 for HCM and Sevasemten for muscular dystrophies. The team is committed to transforming the lives of patients and families affected by these severe muscle diseases.